Molecular Analysis of RAPD-PCR Genomic Patterns in Age Related Acute Myeloid Leukemia

2009 ◽  
Vol 4 (3) ◽  
pp. 35-41 ◽  
Author(s):  
Mohammed A. Ibrahim ◽  
N. Saleh ◽  
Khalida M. Mousawy ◽  
N. Al-Hmoud ◽  
E. Archoukieh ◽  
...  
Blood ◽  
2019 ◽  
Vol 133 (5) ◽  
pp. 446-456 ◽  
Author(s):  
Amina M. Abdul-Aziz ◽  
Yu Sun ◽  
Charlotte Hellmich ◽  
Christopher R. Marlein ◽  
Jayna Mistry ◽  
...  

Abstract Acute myeloid leukemia (AML) is an age-related disease that is highly dependent on the bone marrow (BM) microenvironment. With increasing age, tissues accumulate senescent cells, characterized by an irreversible arrest of cell proliferation and the secretion of a set of proinflammatory cytokines, chemokines, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Here, we report that AML blasts induce a senescent phenotype in the stromal cells within the BM microenvironment and that the BM stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feed back to promote AML blast survival and proliferation via the SASP. Importantly, selective elimination of p16INK4a+ senescent BM stromal cells in vivo improved the survival of mice with leukemia. Next, we find that the leukemia-driven senescent tumor microenvironment is caused by AML-induced NOX2-derived superoxide. Finally, using the p16-3MR mouse model, we show that by targeting NOX2 we reduced BM stromal cell senescence and consequently reduced AML proliferation. Together, these data identify leukemia-generated NOX2-derived superoxide as a driver of protumoral p16INK4a-dependent senescence in BM stromal cells. Our findings reveal the importance of a senescent microenvironment for the pathophysiology of leukemia. These data now open the door to investigate drugs that specifically target the “benign” senescent cells that surround and support AML.


2020 ◽  
Vol 66 (08/2020) ◽  
Author(s):  
Fatma Coskun ◽  
Ferda Percin-Pacal ◽  
Zeliha Emrence ◽  
Muhlis Ar ◽  
Neslihan Abaci ◽  
...  

2001 ◽  
Vol 37 (6) ◽  
pp. 555-556 ◽  
Author(s):  
Der-Cherng Liang ◽  
Lee-Yung Shih ◽  
Chao-Ping Yang ◽  
Iou-Jih Hung ◽  
Shu-Huey Chen ◽  
...  

2018 ◽  
Author(s):  
Raeuf Roushangar ◽  
George I. Mias

In 2018 alone, an estimated 20,000 new acute myeloid leukemia (AML) patients were diagnosed, in the United States, and over 10,000 of them are expected to die from the disease. AML is primarily diagnosed among the elderly (median 68 years old at diagnosis). Prognoses have significantly improved for younger patients, but in patients older than 60 years old as much as 70% of patients will die within a year of diagnosis. In this study, we conducted stratified computational meta-analysis of 2,213 acute myeloid leukemia patients compared to 548 healthy individuals, using curated publicly available data. We carried out analysis of variance of normalized batch corrected data, including considerations for disease, age, tissue and sex. We identified 974 differentially expressed probe sets and 4 significant pathways associated with AML. Additionally, we identified 70 sex- and 375 age-related probe set expression signatures relevant to AML. Finally, we used a machine learning model (KNN model) to classify AML patients compared to healthy individuals with 90+% achieved accuracy. Overall our findings provide a new reanalysis of public datasets, that enabled the identification of potential new gene sets relevant to AML that can potentially be used in future experiments and possible stratified disease diagnostics.


2014 ◽  
Vol 32 (24) ◽  
pp. 2541-2552 ◽  
Author(s):  
Heidi D. Klepin ◽  
Arati V. Rao ◽  
Timothy S. Pardee

Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases.


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